Degradation and Reconstruction of Moenomycin A and Derivatives: Dissecting the Function of the Isoprenoid Chain

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• 作者：Masaatsu Adachi ; Yi Zhang ; Catherine Leimkuhler ; Binyuan Sun ; John V. LaTour ; Daniel E. Kahne
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：November 1, 2006
• 年：2006
• 卷：128
• 期：43
• 页码：14012 - 14013
• 全文大小：59K
• 年卷期：v.128,no.43(November 1, 2006)
• ISSN：1520-5126

文摘

Moenomycin A is the only known natural product that inhibits peptidoglycan biosynthesis by binding the bacterial transglycosylases. We describe a degradation/reconstruction route to manipulate the reducing end of moenomycin A. A comparison of the biological and enzyme inhibitory activity of moenomycin A and an analogue containing a nerol lipid in place of the natural C₂₅ lipid chain provides insight into the role of the moenocinol unit. Our results show that a lipid chain having ten carbons in moenocinol is sufficient for enzyme inhibition, but a longer chain is required for biological acitivity, apparently because the molecule must partition into biological membranes to reach its target in bacterial cells.